Hyaluronic acid encapsulated silver metal organic framework for the construction of a slow-controlled bifunctional nanostructure: Antibacterial and anti-inflammatory in intrauterine adhesion repair

Abstract

Intrauterine adhesion (IUA) is a common gynecological disease caused by endometrial injury, which might result in abnormal menstruation, miscarriage, and even fetal deaths. Nevertheless, existing treatment strategies such as intrauterine device and uterine cavity balloons only provide a physical barrier, and not circumvent inflammation of endometrial microenvironment and retrograde infection. In this study, a slow-controlled bifunctional nanostructure was developed via encapsulating hyaluronic acid (HA) on surface of silver-metal organic framework (Ag-MOF), and then loaded in poly lactic-co-glycolic acid scaffold to prevent IUA. In therapy, macro-molecule of HA provided anti-inflammatory function by the adjustment of signal transduction pathways of macrophage surface receptors, whereas Ag-MOF inactivated bacteria by destroying bacterial membrane and producing reactive oxygen. Significantly, the coated HA effectively avoided burst release of Ag+, thus achieving long-term antibacterial property and good biocompatibility. Antibacterial results showed antibacterial rate of the scaffold reached 87.8 % against staphylococcus aureus. Anti-inflammatory assays showed that the scaffold inhibited the release of inflammatory cytokines and promoted the release of anti-inflammatory cytokines. Moreover, in vitro cell tests revealed that the scaffold effectively inhibited fibroblast growth, indicating its good ability to prevent IUA. Taken together, the scaffold may be a promising candidate for IUA treatment.